TY - JOUR T1 - The Bardet-Biedl Syndrome complex component BBS1 regulates proteasome-dependent F-actin clearance from the centrosome to enable its translocation to the T cell immune synapse JF - bioRxiv DO - 10.1101/2020.11.30.403980 SP - 2020.11.30.403980 AU - Chiara Cassioli AU - Anna Onnis AU - Francesca Finetti AU - Nagaja Capitani AU - Ewoud B Compeer AU - Micheal L Dustin AU - Cosima T Baldari Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/12/01/2020.11.30.403980.abstract N2 - Components of the intraflagellar transport (IFT) system that regulates the assembly of the primary cilium are exploited by the non-ciliated T cell to orchestrate polarized endosome recycling to sustain signaling during immune synapse formation. Here we have investigated the potential role of BBS1, an essential core component of the Bardet-Biedl syndrome complex that cooperates with the IFT system in ciliary protein trafficking, in the assembly of the T cell synapse. We show that BBS1 allows for centrosome polarization towards the immune synapse by promoting its untethering from the nuclear envelope. This function is achieved through the clearance of centrosomal F-actin and its positive regulator WASH, a process that we demonstrate to be dependent on the proteasome. We show that BBS1 regulates this process by coupling the 19S proteasome regulatory subunit to the microtubule motor dynein for its transport to the centrosome. Our data identify the ciliopathy-related protein BBS1 as a new player in T cell synapse assembly that acts upstream of the IFT system to set the stage for polarized vesicular trafficking and sustained signaling.Competing Interest StatementThe authors have declared no competing interest.APCAntigen Presenting CellArlADP Ribosylation Factor LikeArp2/3Actin-Related Protein 2/3 ComplexBBSBardet-Biedl syndromeCRISPRClustered Regularly Interspaced Short Palindromic RepeatsEB-1End-Binding 1F-actinFilamentous actinFIP3Rab11 Family-Interacting Protein 3GFPGreen Fluorescent ProteinGMAP210Golgi Microtubule-Associated Protein 210GPCRG Protein-coupled ReceptorIFTIntraFlagellar TransportISImmune SynapseKDKnock DownKOKnock OutLATLinker for Activation of T cellsLINCLInkers of the Nucleoskeleton and CytoskeletonPASProtein A SepharosePCM-1PeriCentriolar Material-1PCNTPericentrinRT-PCRReverse Transcription Polymerase Chain ReactionsgRNAssmall guide RNAsSAgSuperAntigenSEAStaphylococcal Enterotoxin ASEBStaphylococcal Enterotoxin BSEEStaphylococcal Enterotoxin ESNARESNAP ReceptorShhSonic hedgehogTCRT Cell ReceptorUnc-119Uncoordinated-119VAMPVesicle Associated Membrane ProteinWASHWASP & Scar HomologueWASpWiskott–Aldrich Syndrome proteinWAVEWASP family Verprolin-homologous protein19S RP19S proteasome Regulatory Subunit ER -